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      Animal and human RNA viruses: genetic variability and ability to overcome vaccines

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          Abstract

          RNA viruses, in general, exhibit high mutation rates; this is mainly due to the low fidelity displayed by the RNA-dependent polymerases required for their replication that lack the proofreading machinery to correct misincorporated nucleotides and produce high mutation rates. This lack of replication fidelity, together with the fact that RNA viruses can undergo spontaneous mutations, results in genetic variants displaying different viral morphogenesis, as well as variation on their surface glycoproteins that affect viral antigenicity. This diverse viral population, routinely containing a variety of mutants, is known as a viral ‘quasispecies’. The mutability of their virions allows for fast evolution of RNA viruses that develop antiviral resistance and overcome vaccines much more rapidly than DNA viruses. This also translates into the fact that pathogenic RNA viruses, that cause many diseases and deaths in humans, represent the major viral group involved in zoonotic disease transmission, and are responsible for worldwide pandemics.

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          Most cited references166

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          The distribution of fitness effects caused by single-nucleotide substitutions in an RNA virus.

          Little is known about the mutational fitness effects associated with single-nucleotide substitutions on RNA viral genomes. Here, we used site-directed mutagenesis to create 91 single mutant clones of vesicular stomatitis virus derived from a common ancestral cDNA and performed competition experiments to measure the relative fitness of each mutant. The distribution of nonlethal deleterious effects was highly skewed and had a long, flat tail. As expected, fitness effects depended on whether mutations were chosen at random or reproduced previously described ones. The effect of random deleterious mutations was well described by a log-normal distribution, with -19% reduction of average fitness; the effects distribution of preobserved deleterious mutations was better explained by a beta model. The fit of both models was improved when combined with a uniform distribution. Up to 40% of random mutations were lethal. The proportion of beneficial mutations was unexpectedly high. Beneficial effects followed a gamma distribution, with expected fitness increases of 1% for random mutations and 5% for preobserved mutations.
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            Is Open Access

            ICTV Virus Taxonomy Profile: Picornaviridae

            The family Picornaviridae comprises small non-enveloped viruses with RNA genomes of 6.7 to 10.1 kb, and contains >30 genera and >75 species. Most of the known picornaviruses infect mammals and birds, but some have also been detected in reptiles, amphibians and fish. Many picornaviruses are important human and veterinary pathogens and may cause diseases of the central nervous system, heart, liver, skin, gastrointestinal tract or upper respiratory tract. Most picornaviruses are transmitted by the faecal–oral or respiratory routes. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the taxonomy of the Picornaviridae, which is available at www.ictv.global/report/picornaviridae.
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              Conventional and unconventional mechanisms for capping viral mRNA

              Key Points mRNAs are protected at their 5′ ends by a cap structure consisting of an N7-methylated GTP molecule linked to the first transcribed nucleotide by a 5′–5′ triphosphate bond. The cap structure is essential for RNA splicing, export and stability, and allows the ribosomal complex to recognize mRNAs and ensure their efficient translation. Uncapped RNA molecules are degraded in cytoplasmic granular compartments called processing bodies and may be detected as 'non-self' by the host cell, triggering antiviral innate immune responses through the production of interferons. Conventional RNA capping (that is, of mRNAs from the host cell and from DNA viruses) requires hydrolysis of the 5′ γ-phosphate of RNA by an RNA triphosphatase, transfer of a GMP molecule onto the 5′-end of RNA by a guanylyltransferase, and methylation of this guanosine by an (guanine-N7)-methyltransferase. Subsequent methylations on the first and second transcribed nucleotides by (nucleoside-2′-O)-methyltransferases form cap-1 and cap-2 structures. Viruses have evolved highly diverse capping mechanisms to acquire cap structures using their own or cellular capping machineries, or by stealing cap structures from cellular mRNAs. Virally encoded RNA-capping machineries are diverse in terms of their genetic components, protein domain organization, enzyme structures, and reaction mechanisms and pathways, making viral RNA capping an attractive target for antiviral-drug design.
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                Author and article information

                Contributors
                tomas.gonzalez@usc.es
                Journal
                Arch Microbiol
                Arch. Microbiol
                Archives of Microbiology
                Springer Berlin Heidelberg (Berlin/Heidelberg )
                0302-8933
                1432-072X
                28 September 2020
                : 1-22
                Affiliations
                [1 ]GRID grid.11794.3a, ISNI 0000000109410645, Department of Microbiology, Faculty of Pharmacy, , University of Santiago de Compostela, ; 5706 Santiago de Compostela, Spain
                [2 ]GRID grid.1013.3, ISNI 0000 0004 1936 834X, Sydney School of Veterinary Science, Faculty of Science, , University of Sydney, ; Sydney, NSW 2006 Australia
                Author notes

                Communicated by Erko stackebrandt.

                Author information
                http://orcid.org/0000-0002-9282-6234
                Article
                2040
                10.1007/s00203-020-02040-5
                7521576
                32989475
                d5ca56bd-ebc7-4f2a-8d08-a3b5ed147111
                © Springer-Verlag GmbH Germany, part of Springer Nature 2020

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 18 April 2020
                : 29 June 2020
                : 12 September 2020
                Categories
                Mini-Review

                Microbiology & Virology
                rna viruses,viral rna polymerases,viral genetic variability,viral vaccines

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